Thermodynamics of writhe in DNA minicircles from molecular dynamics simulations.

DNA supercoiling plays a role in genetic control by imposing torsional stress. This can induce writhe, which changes the global shape of the DNA. We have used atomistic molecular dynamics simulations to partition the free energy changes driving the writhing and unwrithing transitions in supercoiled minicircle DNA. The calculations show that while writhing is energetically driven, the unwrithing transition occurs because the circular state has a higher configurational entropy than the plectoneme. Writhing improves the van der Waals interactions between stacked bases, but can be suppressed by electrostatic repulsion within the negatively charged backbone strands in low salt conditions where electrostatic screening is poor. The free energy difference between circular and plectonemic DNA is determined by such a delicate balance of opposing thermodynamic terms that any perturbation in the environment, such as a change in salt concentration, can be sufficient to convert between these two states. This switchable behavior provides a mechanism for supercoiled DNA to store and communicate biological information physically as well as chemically.